Dry environment on the expression of lacrimal gland S100A9,Anxa1,and Clu in rats via proteomics

●AIM:To investigate the underlying mechanism of dry environment(autumn dryness)affecting the lacrimal glands in rats.●METHODS:Twenty Sprague-Dawley rats were randomly divided into two groups.The rats were fed in specific pathogen free environment as the control group(n=10),and the rats fed in dry environment as the dryness group(n=10).After 24d,lacrimal glands were collected from the rats.The tissues morphology was observed by hematoxylineosin(HE)staining.Tandem mass tags(TMT)quantitative proteomics analysis technology was used to screen the differential expressed proteins of lacrimal glands between the two groups,then bioinformatics analysis was performed.Further,the immunohistochemical(IHC)method was used to verify the target proteins.●RESULTS:In dryness group,the lacrimal glands lobule atrophied,the glandular cavities enlarged,the sparse nuclear distribution and scattered inflammatory infiltration between the acinus were observed.The proteomics exhibited that a total of 195 up-regulated and 236 downregulated differential expressed proteins screened from the lacrimal glands of rats.It was indicated that the biological processes(BP)of differential expressed proteins mainly included cell processes and single BP.The cellular compositions of differential expressed proteins mainly located in cells,organelles.The molecular functions of differential expressed proteins mainly included binding,catalytic activity.Moreover,the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis showed that the differential expressed proteins mainly involved lysosome,complement and coagulation cascade,and ribosome pathway.The IHC result verified that the up-regulated expression proteins of Protein S100A9(S100A9),Annexin A1(Anxa1),and Clusterin(Clu)in lacrimal glands of rats in dryness group were higher than control group.●CONCLUSION:The up-regulated expression proteins of S100A9,Anxa1,and Clu may be the potential mechanisms of dry eye symptoms caused by dry environment.This study provides clues of dry environments causing eye-related diseases for further studies.

Pro-inflammatory cytokines levels in tears and dry eye disease in Parkinson’s disease

Background:Neuroinflammation is an essential event in Parkinson’s disease(PD).Identifying affordable and less invasive biomarkers to make an early diagnosis and monitor therapeutic strategies should be a priority among researchers.The study’s objective was to measure tear levels of cytokines in subjects with PD and their association with motor features and the presence of dry eye symptoms.Methods:A total of 16 subjects with PD and 16 age-and sex-matched controls were included.Movement Disorders Society-Unified Parkinson’s Disease Rating Scale(MDS-UPDRS),Hoehn and Yahr(HY)stage scale,Montreal Cognitive Assessment(MoCA),tear break-up time(TBUT),blink rate(BR),Dry Eye Questionnaire 5(DEQ-5)were examined,and pro-inflammatory cytokines[interleukin(IL)-1β,IL-6,IL-8,IL-10,IL-12p70 and tumor necrosis factor-alpha(TNF-α)]were quantified in tears using the BD Cytometric Bead Array Human Inflammatory Cytokine Kit.Results:Higher tear TNF-αwere quantified in PD compared to controls(2.94±3.95 vs.0.33±0.49 pg/mL,P=0.008).According to DEQ-5,50.0%(n=8)of PD subjects and 12.5%(n=2)controls had dry eye disease(DED).No differences were found in cytokines concentrations between PD patients with DED compared to those without DED.IL-8 was associated with the HY stage,TBUT,DEQ-5,and a better MoCA score.A higher BR correlated moderately with a lower HY stage(r=−0.645,P=0.007),and DED patients have lower BR in PD(12.14±2.54 vs.9.0±2.06 blinks/minute,P=0.031).Conclusions:PD patients have higher levels of TNF-αin tears than age-and sex-matched HC.IL-8 in tears may be both involved in the severity of the disease and in the development of DED in PD.In addition,our findings suggest that as HY stage increases,indicating a more advanced stage,BR decreases,indicating greater motor impairment.Conversely,the presence of DED is associated with higher levels of bradykinesia in PD patients,suggesting a potential relationship between DED and motor impairment severity.

Comparison of corneal biomechanics in Sjogren's syndrome and non-Sjogren's syndrome dry eyes by Scheimpflug based device

AIM：To compare the corneal biomechanics of Sj？gren＇s syndrome（SS） and non-SS dry eyes with Corneal Visualization Scheimpflug Technology（CorV is ST）.METHODS：Corneal biomechanics and tear film parameters, namely the Schirmer I test value, tear film break-up time（TBUT） and corneal staining score（CSS） were detected in 34 eyes of 34 dry eye patients with SS（SSDE group） and 34 dry eye subjects without SS（NSSDE group） using CorV is ST. The differences of the above parameters between the two groups were examined, and the relationship between corneal biomechanics and tear film parameters were observed. RESULTS：The differences in age, sex, intraocular pressure（IOP） and central corneal thickness（CCT） were not significant between the two groups（P〉0.05）. The tear film parameters had significant differences between the SSDE group and NSSDE group（all P〈0.05）. Patients in the SSDE group had significantly lower A1-time and HC-time, but higher DA（P=0.01, 0.02, and 0.02, respectively） compared with the NSSDE group. In the SSDE group, DA was negatively correlated with TBUT（rho=-0.38, P=0.03）; HC-time was negatively correlated with CSS（rho=-0.43, P=0.02）. In the NSSDE group, HC-time was again negatively correlated with CSS（rho=-0.39, P=0.02）.CONCLUSION：There are differences in corneal biomechanical properties between SSDE and NSSDE. The cornea of SSDE tends to show less ＂stiffness＂, as seen by a significantly shorter A1-time and HC-time, but larger DA, compared with the cornea of NSSDE. Biomechanical parameters can be influenced by different tear film parameters in both groups.

Corneal sensitivity,ocular surface health and tear film stability after punctal plug therapy of aqueous deficient dry eye

AIM： To evaluate the effect of punctal occlusion using thermosensitive（smart plug） versus silicone plug for management of aqueous deficient dry eye on cornea sensitivity, ocular surface health and tear film stability.METHODS： A comparative prospective interventiona case study included 45 patients with bilateral severe form of aqueous deficient dry eye. In each patient, the smar plug was inserted in the lower punctum of the right eye which was considered as study group 1 and silicone plug was inserted in the lower punctum of the left eye o the same patient which was considered as study group2. All patients were subjected to careful history taking and questionnaire for subjective assessment of severity of symptoms. Corneal sensitivity, corneal fluorescein rose bengal staining, Schirmer＇s I test, tear film break up time and conjunctival impression cytology were performed pre and 1, 3 and 6mo post plug insertion.RESULTS： A statistically significant improvement in subjective and objective manifestations occurred following treatment with both types of plugs（P 〈0.01）The thermosensitive plug caused significant overal improvement, decrease in frequency of application o tear substitutes and improvement of conjunctiva impression cytology parameters in the inserted side（P 〈0.01）. Canaliculitis was reported in two eyes（4.4% following punctal occlusion using thermosensitive plug（study group 1）. Spontaneous plug loss occurred in 21eyes（46.6%） in the silicone plug group（study group 2）.CONCLUSION： Improvement of subjective and objective manifestations of aqueous deficient dry eye occurs following punctal plug occlusion. Thermosensitive plug has good patient＇s compliance with fewer complications and lower rates of loss compared to the silicone plug.

Topical biological agents targeting cytokines for the treatment of dry eye disease

Because inflammation plays a key role in the pathogenesis of dry eye disease and Sjogren's syndrome, topical anti-inflammatory agents such as corticosteroids and cyclosporine A have been used to treat inflammation of the ocular surface and lacrimal gland. Systemic biological agents that target specific immune molecules or cells such as tumor necrosis factor(TNF)-α, interferone-α, interleukin(IL)-1, IL-6, or B cells have been used in an attempt to treat Sjogren's syndrome. However, the efficacy of systemic biological agents, other than B-cell targeting agents, has not yet been confirmed in Sjogren's syndrome. Several studies have recently evaluated the efficacy of topical administration of biological agents targeting cytokines in the treatment of dry eye disease. Topical blockade of IL-1 by using IL-1 receptor antagonist could ameliorate clinical signs and inflammation of experimental dry eye. Using a mouse model of desiccating stress-induced dry eye, we have demonstrated that topical application of a TNF-α blocking agent, infliximab, could improve tear production and ocular surface irregularity, decrease inflammatory cytokines and Th-1 CD4+ cells on the ocular surface, and increase gobletcell density in the conjunctiva. Although controversy still remains, the use of topical biological agents targeting inflammatory cytokines may be a promising therapy for human dry eye disease.

Visual resolution under photopic and mesopic conditions in patients with Sjogren's syndrome

AIM:To focus on different visual resolution tasks under photopic and mesopic conditions in Sjogren’s syndrome patients compared to age-matched healthy controls.METHODS:The visual resolution measurements included high and low visual acuities and contrast sensitivity functions.These tests were conducted under photopic and then mesopic conditions.Twenty-one Sjögren’s syndrome patients and 21 aged-matched healthy volunteers completed all the measurements in this study.RESULTS:Sjogren’s syndrome patients have greater impairment in contrast sensitivity than standardized visual acuity.This reduction was significant under the mesopic condition.Also,Sjogren’s syndrome patients treated with pilocarpine suffer more than patients without pilocarpine treatment under low light conditions.CONCLUSION:Sjogren’s syndrome patients shows greater impairment in different visual resolution tasks due to dry eye symptoms.

Gastrointestinal microbiome and primary Sjogren’s syndrome: a review of the literature and conclusions

The recognition of the profound impact of the human gastrointestinal microbiome(GM) on human autoimmune diseases has gradually increased thanks to deeper research efforts. As a systemic autoimmune disease, primary Sjogren’s syndrome(pSS) cannot be completely cured. Human studies have revealed that GM species and diversity are altered in patients with p SS compared with healthy individuals. Animal studies have provided possible mechanisms for the association between pSS and GM. The potential role of GM in pSS is exerted through several mechanisms. GM dysbiosis leads to increased intestinal permeability, which increases the risk of GM antigen exposure and activates specific autoreactive T lymphocytes via “molecular mimicry”. In addition, GM antigen exposure and intestinal immune tolerance loss caused by GM dysbiosis together induce chronic local gut mucosal inflammation, which deteriorates to systemic chronic non-specific inflammation with the circulation of pro-inflammatory lymphocytes and cytokines. These factors eventually activate autoreactive B lymphocytes and lead to pSS. If GM plays a key role in the pathogenesis of pSS, clarifying the underlying mechanisms will be helpful for the development of new therapies targeting GM for dry eye associated with pSS. This review summarizes the latest knowledge about the relationship between GM and p SS,with the aim of contributing to future research and to the development of new clinical applications.

In pursuit of objective dry eye screening clinical techniques

Dry eye is a multifactorial,progressive,and chronic disease of the tears and ocular surface.The disease is multi-factorial and has intermittent symptoms.Discomfort,visual disturbance,tear film instability with potential damage to the ocular surface,and increased tear film osmolarity are known associates.Dry eye is a common clinical problem for eye-care providers worldwide and there is a large number of clinical investigative techniques for the evaluation of dry eye.Despite this,however,there is no globally accepted guideline for dry eye diagnosis and none of the available tests may hold the title of the‘gold standard’.The majority of the techniques involved in the diagnosis of the disease,particularly for its early stages,has a large degree of subjectivity.The purpose of this article is to review existing dry eye investigative techniques and to present a new objective dry eye screening technique based on optical coherence tomography.